Pages

Friday, May 17, 2013

Angelina Jolie's breasts, SNPs, and Jmol

I never had thought I would ever blog about Angelina Jolie's breasts, but they were the news this week that turns out to help me answer a student question for our bioinformatics course. The question was about how to visualize SNPs in 3D protein structures. The link is the protein encoded by BRCA1. Some SNPs in BRCA1 are strongly (cor)related to cancer, as you can read about in OMIM. One 3D protein structure in the pdb.org is 1JM7, which is a solution based on NMR experiments by Brzovic et al. (doi:10.1038/nsb1001-833).

The Sequence tab for this structure provides us the sequences of the two proteins in this structure, one of which is BRCA1. We can add the SNP annotation with the drop down box:

(BTW, not all structures have SNP information, so this drop down box option is not always present!)

It will show that very many SNPs are known. OMIM needs to be checked to see if they are associated with disease. It should look like this:

You can see the "Single Nucleotide row, with many colored SNPS circles. The first is Met1 and the second is Arg7. This post is, however, on how to visualize the SNPs in Jmol. Now, the Jmol applet is linked to on the pdb.org website, on the right side in the same Sequence tab:

If you click the "Display Jmol" option, the Jmol applet should fire up (your browser does require the Java plugin). That will create a small dialog hovering over that corner with the Jmol applet. You can right-click on the background and select the Console option:

That will fire up another dialog window, one that will look like the one below and in the lower large section we can write command (yes, some minimal programmaing, in Jmol script!). For example, we can select the methionine at position 1 (the first SNP from BRCA1 as found earlier):

Where select Met1 is typed, you type that too, and press enter. You have now selected 266 atoms as will be written in the top large text area. Then you type the following two further commands, and notice the effect in the Jmol applet window, creating a set of three commands:

select Met1

spacefill on

color green

Then, for each SNP you can pick a different color, and easily visualize a set of SNPs. Now, among all the variants it reports missense SNPs for Cys61 and Cys64. So, the following six commands will visualize these two SNPs, with Cys61 in red, and Cys64 in green:

select Cys61

spacefill on

color red

select Cys64

spacefill on

color green

There are some additonal zinc ions in the structure, which you can color orange with:

select zinc

color orange

This will create this view in Jmol:

So, you can clearly see that the two cysteines affected by the SNPs are involved in the structure's zinc finger. No wonder those mutations give trouble.

Search This Blog

This blog deals with chemblaics in the broader sense. Chemblaics (pronounced chem-bla-ics) is the science that uses computers to solve problems in chemistry, biochemistry and related fields. The big difference between chemblaics and areas such as chem(o)?informatics, chemometrics, computational chemistry, etc, is that chemblaics only uses open source software, open data, and open standards, making experimental results reproducible and validatable. And this is a big difference!

About Me

Assistant professor at the Dept of Bioinformatics - BiGCaT at NUTRIM, Maastricht University, studying biology at an unsupervised and atomic level. Open Science is my main hobby resulting in participation in, among many others, Bioclipse, CDK and WikiPathways. ORCID:0000-0001-7542-0286. Posts on G+ are personal.

Cookies

In the EU there is a directive upcoming requiring websites to warn people about HTTP cookies. This website uses the Blogger.com platform, Google Adsense (not that is it actually paying anything significantly), and a few scripts to count how often a blog post was tweeted, using Topsy and LinkedIn. These services undoubtedly make use of cookies, which you can disallow in your browser.